Nasal administration of calcium channel, blockers for treatment of hypertension and other cardiovascular disorders

Abstract

Pharmaceutical compositions useful for the treatment of cardiovascular disorders such as hypertension are described. These compositions are formulated for nasal administration and comprise a therapeutically effective amount of a calcium channel blocker, optionally a pharmaceutically acceptable carrier that is suitable for nasal administration, and one or more optional members selected from excipients and additional pharmaceutically active agents.

1 . A method of increasing the amount of a calcium channel blocker delivered to the brain of a patient suffering from hypertension, comprising nasally administering a pharmaceutical composition comprising a therapeutically effective amount of the calcium channel blocker.  
     
     
         2 . The method of  claim 1 , wherein the calcium channel blocker is selected from verapamil, diltiazem, cinnarizine, and nifedipine.  
     
     
         3 . The method of  claim 1 , wherein the calcium channel blocker represents about 0.2% to about 30% by weight of the composition.  
     
     
         4 . The method of  claim 3 , wherein the calcium channel blocker represents about 2% to about 20% by weight of the composition.  
     
     
         5 . The method of  claim 1 , wherein the composition further comprises a pharmaceutically acceptable carrier that is suitable for nasal drug administration.  
     
     
         6 . The method of  claim 5 , wherein the composition is administered in the form of an aerosol nasal spray.  
     
     
         7 . The method of  claim 6 , wherein the carrier is a propellant.  
     
     
         8 . The method of  claim 5 , wherein the composition is administered in the form of a liquid.  
     
     
         9 . The method of  claim 8 , wherein the carrier is purified water, saline, buffer, or a combination of any of the foregoing.  
     
     
         10 . The method of  claim 1 , wherein the composition is administered in the form of a dry powder.  
     
     
         11 . The method of  claim 5 , wherein the composition is administered in the form of a dry powder.  
     
     
         12 . The method of  claim 11 , wherein the carrier is selected from fructose, galactose, glucose, lactitol, lactose, maltitol, maltose, mannitol, melezitose, myoinositol, palatinite, raffinose, stachyose, sucrose, trehalose, xylitol, as well as hydrates thereof, and combinations of any of the foregoing.  
     
     
         13 . The method of  claim 12 , wherein the carrier is lactose.  
     
     
         14 . The method of  claim 1 , wherein the composition is administered in a unit dosage form containing the calcium channel blocker in an amount of about 0.2 to about 20 mg of the composition.  
     
     
         15 . The method of  claim 1 , wherein the composition further comprises a therapeutically effective amount of at least one additional pharmaceutically active agent.  
     
     
         16 . The method of  claim 15 , wherein the additional active agents are selected from diuretics, β-blockers, ACE inhibitors, angiotensin II receptor blockers, adrenergic inhibitors, and vasodilators.  
     
     
         17 . The method of  claim 1 , wherein the composition is formulated to provide timed release.  
     
     
         18 . The method of  claim 1 , wherein the composition is formulated to provide sustained release.  
     
     
         19 . The method of  claim 1 , wherein the composition is formulated to provide controlled release.  
     
     
         20 . The method of  claim 1 , wherein the composition further comprises at least one excipient.  
     
     
         21 . The method of  claim 20 , wherein the excipient is a bioadhesive material.  
     
     
         22 . The method of  claim 21 , wherein the bioadhesive material is selected from Carbopol, methylcellulose, hydroxypropyl methylcellulose, hydroxyethylcellulose, hydroxypropylcellulose, sodium carboxymethylcellulose, polyvinyl alcohol, polyvinylpyrrolidone, polyacrylates, polyacrylamide, dextran, gellan gum, poloxamer, calcium polycarbophil, cellulose acetate phthalate, sodium hyaluronate, hyaluronic acid and alginate, chitosan.  
     
     
         23 . The method of  claim 20 , wherein the excipient is a permeation enhancer.  
     
     
         24 . A method of treating a patient suffering from hypertension comprising targeting delivery of a calcium channel blocker to the brain of the patient by administering the calcium channel blocker intranasally.  
     
     
         25 . An improved method of treating a cardiovascular disorder with a calcium channel blocker; the improvement comprising administering the calcium channel blocker nasally to maximize the amount of calcium channel blocker reaching the brain and to minimize peripherally mediated adverse events.  
     
     
         26 . A method of  claim 25 , wherein the cardiovascular disorder is hypertension.  
     
     
         27 . A pharmaceutical composition formulated for nasal drug administration, comprising: a therapeutically effective amount of the calcium channel blocker selected from cinnarizine, and nifedipine.  
     
     
         28 . The composition of  claim 27 , wherein the composition further comprises a pharmaceutically acceptable carrier that is suitable for nasal drug administration.  
     
     
         29 . The composition of  claim 28 , wherein the composition is administered in the form of an aerosol nasal spray.  
     
     
         30 . The composition of  claim 29 , wherein the carrier is a propellant.  
     
     
         31 . The composition of  claim 28 , wherein the composition is administered in the form of a liquid.  
     
     
         32 . The composition of  claim 31 , wherein the carrier is purified water, saline, buffer, or a combination of any of the foregoing.  
     
     
         33 . The composition of  claim 27 , wherein the composition is administered in the form of a dry powder.  
     
     
         34 . The composition of  claim 28 , wherein the composition is administered in the form of a dry powder.  
     
     
         35 . The composition of  claim 34 , wherein the carrier is selected from fructose, galactose, glucose, lactitol, lactose, maltitol, maltose, mannitol, melezitose, myoinositol, palatinite, raffinose, stachyose, sucrose, trehalose, xylitol, as well as hydrates thereof, and combinations of any of the foregoing.  
     
     
         36 . The composition of  claim 27 , wherein the composition further comprises a therapeutically effective amount of at least one additional pharmaceutically active agent.  
     
     
         37 . The composition of  claim 27 , wherein the composition is formulated to provide timed release.  
     
     
         38 . The composition of  claim 27 , wherein the composition is formulated to provide sustained release.  
     
     
         39 . The composition of  claim 27 , wherein the composition is formulated to provide controlled release.  
     
     
         40 . The composition of  claim 27 , wherein the composition further comprises at least one excipient.  
     
     
         41 . The composition of  claim 40 , wherein the excipient is a bioadhesive material.  
     
     
         42 . The composition of  claim 40 , wherein the excipient is a permeation enhancer.  
     
     
         43 . A nasal administrable drug delivery device, comprising: the composition of  claim 28  and a means for housing and dispensing unit dosages of the composition into a nasal passage of a patient.  
     
     
         44 . The device of  claim 43 , comprising a dry powder inhaler, metered-dose inhaler, medicine dropper, or pump spray bottle.